Service d'Obstétrique-Maternité, Chirurgie, Médecine et Imagerie Fœtales, Hôpital Necker Enfants Malades, GHU Paris Centre, AP-HP, F-75015 Paris, France.
Équipe d'Accueil «FŒTUS» 73-28, Université Paris Cité, F-75015 Paris, France.
Viruses. 2022 Sep 28;14(10):2145. doi: 10.3390/v14102145.
Congenital cytomegalovirus (cCMV) infection is frequent and potentially severe. The immunobiology of cCMV infection is poorly understood, involving cytokines that could be carried within or on the surface of extracellular vesicles (EV). We investigated intra-amniotic cytokines, mediated or not by EV, in cCMV infection.
Forty infected fetuses following early maternal primary infection and forty negative controls were included. Infected fetuses were classified according to severity at birth: asymptomatic, moderately or severely symptomatic. Following the capture of EV in amniotic fluid (AF), the concentrations of 38 cytokines were quantified. The association with infection and its severity was determined using univariate and multivariate analysis. A prediction analysis based on principal component analysis was conducted.
cCMV infection was nominally associated with an increase in six cytokines, mainly soluble (IP-10, IL-18, ITAC, and TRAIL). EV-associated IP-10 was also increased in cases of fetal infection. Severity of fetal infection was nominally associated with an increase in twelve cytokines, including five also associated with fetal infection. A pattern of specific increase in six proteins fitted severely symptomatic infection, including IL-18soluble, TRAILsoluble, CRPsoluble, TRAILsurface, MIGinternal, and RANTESinternal.
Fetal infection and its severity are associated with an increase in pro-inflammatory cytokines involved in Th1 immune response.
先天性巨细胞病毒（cCMV）感染较为常见，且可能较为严重。cCMV 感染的免疫生物学尚未完全阐明，涉及细胞因子，这些细胞因子可能存在于细胞外囊泡（EV）内部或表面。我们研究了 cCMV 感染时羊水（AF）中细胞因子的变化，这些细胞因子可能与 EV 有关，也可能与 EV 无关。
本研究纳入了 40 例因早期母体原发感染而致胎儿感染的病例，以及 40 例阴性对照。根据出生时的严重程度对感染胎儿进行分类：无症状、中度或重度症状。对 EV 进行捕获后，定量分析了 38 种细胞因子的浓度。采用单变量和多变量分析确定感染及其严重程度的相关性。此外，还进行了基于主成分分析的预测分析。
cCMV 感染与 6 种细胞因子的增加有关，主要是可溶性细胞因子（IP-10、IL-18、ITAC 和 TRAIL）。EV 相关的 IP-10 在胎儿感染时也增加。胎儿感染的严重程度与 12 种细胞因子的增加有关，其中 5 种也与胎儿感染有关。在严重症状感染中，有 6 种蛋白出现了特定的增加模式，包括可溶性 IL-18、可溶性 TRAIL、可溶性 CRP、TRAIL 表面、MIG 内部和 RANTES 内部。
胎儿感染及其严重程度与 Th1 免疫反应相关的促炎细胞因子增加有关。
